Phenylephrine tannate compositions are well known and are widely used as antihistamines alone or in combination with other antihistamines such as chlorpheniramine tannate and pyrilamine tannate. Phenylephrine as the free base has a melting point of 169.degree.-172.degree. C. and may be prepared from m-hydroxy-.omega.-chloroacetophenone and methylamine, see U.S. Pat. Nos. 1,932,947 and 1,954,389.
Tannic acid, also known as tannin, is a well known naturally occurring substance. Commercially available tannic acid usually contains about 5 wt. % water, has a molecular weight of about 1700 and is typically produced from Turkish or Chinese nutgall.
Commercially available phenylephrine tannate compositions are relatively impure. Such compositions are prepared by reacting the phenylephrine free base with tannic acid in the presence of a volatile solvent, typically isopropanol. The yield is only fair (e.g. about 70%) and a significant amount of the volatile solvent, e.g. 6-10 wt. %, based on the weight of the composition, remains with the product and cannot be removed.
Typically, in the conventional isopropanol route, the phenylephrine free base and the tannic acid will be present in the isopropanol at a concentration of about 20 wt. %, based on the weight of the reaction mixture.
The reaction mixture is stirred for about one hour, while maintaining a temperature of 60.degree.-70.degree. C. The reaction mixture is cooled to room temperature and filtered. The precipitate is vacuum-dried for an extended period of time at a temperature of 60.degree.-80.degree. C. A yield of product of only about 70 % is obtained and the product purity will only be about 90 wt. % at best (the impurities will consist of isopropanol and degradation products which cannot be removed); the density of the product will be about 0.45 g/cc.
Phenylephrine tannate is quite heat sensitive and it therefore undergoes decomposition quite readily upon prolonged exposures to temperatures as low as 50.degree. C. Accordingly, even when the solvent utilized in its preparation has a relatively high vapor pressure such as is in the case of isopropanol, it is impossible to reduce the solvent content below about 6 wt. %, based on the weight of the phenylephrine composition, even at reduced pressures and very mild elevated temperatures. Moreover, from an environmental point, it would be most desirable if phenylephrine tannate could be prepared such that the use of volatile solvents could be avoided.